Guhong Injection For Cerebral Ischemia:the Effectiveness And Mechanism

Background:Stroke is one of the most common causes of mortality and disease burden worldwide.67.3～80.5%of strokes are ischemic stroke. The effectiveness of Guhong injection for acute ischemic stroke is proved by several clinical trials. The effectiveness and mechanism of Guhong injection for cerebral ischemia in animal experiment are not clear.Objective:To evaluate the effectiveness and mechanism of Guhong injection for cerebral ischemia.Methods:Two models of cerebral ischemia, permanent bilateral carotid artery occlusion (2VO) and middle cerebral artery occlusion (MCAO) were used in our study. Aceglutamine, safflower and Guhong injection were evaluated in each model. For2VO, behavior changes were evaluated by open field test, Morris water maze test and Y maze test. The changes of neurons and microglia in hippocampus region CA1were evaluated by NeuN and Ibal staining separately. The initial evaluation of the neurogenesis in dentate gyrus was done by BrdU staining. Several synapsis-related genes were evaluated by real time PCR. For MCAO, behavior changes were evaluated by neurologic deficit scores, adhesive removal test, balance beam test and shuttle box test. TTC staining was used to demonstrate the cerebral infarction.Result:For2VO, the2VO surgery increased the escape latency in Morris water maze test (P<0.001), and decreased the number of neurons in hippocampus region CA1(P<0.001) significantly. Open field test (P=0.577), Y maze test (P=0.547), BrdU positive cells in DG (P=0.052), microglia in region CA1(P=0.750) and the synapsis-related gene tested were not significantly affected by the surgery. Aceglutamine, safflower and Guhong injection seemed to protect the neurons in region CA1(P<0.001, respectively), although their protective effect was not showed by Morris water maze test (P=0.282). For MCAO, the neurologic deficit scores (P<0.001), the asymmetric index in adhesive removal test (P=0.010), the beam walking latency (P=0.003) and the relative infarction volume (P=0.037) were significantly increased by MCAO surgery. The result of shuttle box was not significantly affected by the surgery (latency:P=0.952, counts:P=0.905). The beam walking latency was significantly decreased by Guhong injection (P=0.010), and was not significantly affected by aceglutamine (P=0.139) or safflower (P=0.093). The neurologic deficit scores (P=0.568), the asymmetric index in adhesive removal test (P=0.688), and relative infarction volume (P=0.350) were unaffected by Guhong injection, aceglutamine or safflower.Conclusion:Guhong injection, as well as aceglutamine and safflower injection, showed protective effect on neurons in region CA1for chronic cerebral ischemia. Guhong injection seemed to improve the behavior results for acute cerebral ischemia. Aceglutamine and safflower, on the other hand, didn’t show protective effect for acute cerebral ischemia.